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Background and Rationale: Polycyclic aromatic hydrocarbons are a lipophilic group of pollutants that persist in the atmosphere for long periods, constituting a permanent source of exposure for humans. They have been associated, for a long time, with the risk in developing breast cancer, but there are still unresolved questions. Conclusion: Integrated strategies are required that should consider molecular and population-level studies, to understand and elaborate approaches to prevent the risks in developing breast cancer. [ABSTRACT FROM AUTHOR]

The monocyte-macrophage lineage shows a high degree of diversity and plasticity. Once they infiltrate tissues, they may acquire two main functional phenotypes, being known as the classically activated type 1 macrophages (M1) and the alternative activated type 2 macrophages (M2). The M1 phenotype can be induced by bacterial products and interferon-γ and exerts a cytotoxic effect on cancer cells. Conversely, the alternatively activated M2 phenotype is induced by Il-4/IL13 and promotes tumor cell growth and vascularization. Although receptor for advanced glycation end-products (RAGE) engagement in M1 macrophages has been reported by several groups to promote inflammation, nothing is known about the functionality of RAGE in M2 macrophages. In the current study, we demonstrate that RAGE is equally expressed in both macrophage phenotypes and that RAGE activation by high-mobility group protein box1 (HMGB1) promotes protumoral activities of M2 macrophages. MKN45 cells co-cultured with M2 macrophages treated with HMGB1 at different times displayed higher invasive abilities. Additionally, conditioned medium from HMGB1-treated M2 macrophages promotes angiogenesis in vitro. RAGE-targeting knockdown abrogates these activities. Overall, the present findings suggest that HMGB1 may contribute, by a RAGE-dependent mechanism, to the protumoral activities of the M2 phenotype. [ABSTRACT FROM AUTHOR]

Background: Previous studies have demonstrated that geranyl metabolites, found mainly in marine organisms, exhibit interesting antimicrobial and antifungal activities. In addition, linear geranyl derivatives have been synthesized as drugs and reported cytotoxic and anticancer activities. Aims: Considering the biological testing and the structural features of these compounds, we evaluated seven linear geranylphenol derivatives on the human breast cancer cell line MDA-MB-231, and the human gastric cancer cell line MKN74. Results: We found that compounds 2, 5 and 7 were cytotoxic for both cancer cell lines. From them, the most potent was compound 2, with an IC50=7.5 µM for MKN74 cells, and compound 7, with an IC50=14.73 µM for MDA-MB-231 cells. By nuclear staining and inmunocytochemistry, we detected that the three compounds induced cell death, and by Western blot analysis, we observed a remarkable decrease in the expression of cyclin D1 and the retinoblastoma protein, key regulators of the cell cycle. Conclusion: Considering that compounds 2 and 7 were the most potent compounds inducing cell death, and were able to decrease the expression of retinoblastoma protein and cyclin D1, proteins usually altered in different types of cancers, they appear as promising therapeutic agents against cancer. [ABSTRACT FROM AUTHOR]

The monocyte-macrophage lineage shows a high degree of diversity and plasticity. Once they infiltrate tissues, they may acquire two main functional phenotypes, being known as the classically activated type 1 macrophages (M1) and the alternative activated type 2 macrophages (M2). The M1 phenotype can be induced by bacterial products and interferon-γ and exerts a cytotoxic effect on cancer cells. Conversely, the alternatively activated M2 phenotype is induced by Il-4/IL13 and promotes tumor cell growth and vascularization. Although receptor for advanced glycation end-products (RAGE) engagement in M1 macrophages has been reported by several groups to promote inflammation, nothing is known about the functionality of RAGE in M2 macrophages. In the current study, we demonstrate that RAGE is equally expressed in both macrophage phenotypes and that RAGE activation by high-mobility group protein box1 (HMGB1) promotes protumoral activities of M2 macrophages. MKN45 cells co-cultured with M2 macrophages treated with HMGB1 at different times displayed higher invasive abilities. Additionally, conditioned medium from HMGB1-treated M2 macrophages promotes angiogenesis in vitro. RAGE-targeting knockdown abrogates these activities. Overall, the present findings suggest that HMGB1 may contribute, by a RAGE-dependent mechanism, to the protumoral activities of the M2 phenotype.